Donor Human Milk Versus Preterm Formula for Feeding Preterm and Very Low Birth Weight Infants: An Umbrella Review and Meta-Analytic Re-Analysis

OBJECTIVE: To systematically synthesize and critically appraise the available meta-analytic evidence comparing donor human milk with formula feeding in preterm and VLBW infants using an umbrella review and meta-analytic re-analysis. METHODS: A comprehensive search of PubMed, Web of Science, and the Cochrane Database of Systematic Reviews was conducted from database inception to March 2026. Systematic reviews with meta-analyses comparing donor human milk and formula feeding in preterm or VLBW infants were included. Methodological quality was assessed using AMSTAR-2, overlap among primary studies was quantified using the Corrected Covered Area (CCA), and eligible outcomes were re-analyzed using random-effects models. RESULTS: Four meta-analyses met the inclusion criteria. Methodological quality ranged from critically low to moderate, and a very high degree of overlap among primary studies was identified (CCA = 52.38%). Meta-analytic re-analysis demonstrated that donor human milk significantly reduced the risk of necrotizing enterocolitis compared with formula feeding (pooled effect size = 0.50, 95% CI 0.21-0.79). Formula-fed infants achieved significantly greater weight gain (pooled effect size = -3.45, 95% CI -3.68 to -3.22), whereas no significant differences were observed for length gain (pooled effect size = 0.24, 95% CI -0.68 to 1.15) or head circumference growth (pooled effect size = 0.18, 95% CI -0.42 to 0.79). CONCLUSIONS: Donor human milk provides substantial protection against necrotizing enterocolitis in preterm and VLBW infants while achieving growth outcomes comparable to formula for linear growth and head circumference. Despite slower short-term weight gain, current evidence supports donor human milk as the preferred alternative when the mother's own milk is unavailable. However, the very high overlap among primary studies and the methodological limitations of existing meta-analyses highlight the need for higher-quality evidence syntheses and additional well-designed randomized controlled trials.